Content uploaded by Reg J Fletcher
Author content
All content in this area was uploaded by Reg J Fletcher on Jun 17, 2018
Content may be subject to copyright.
Title: Systematic review and meta-analysis of data relating to wheat bran intake and blood
lipids, specifically triglycerides.
Authors:
Jolene McMonagle PhD1, , Reg J. Fletcher 1, Janice I. Harland PhD2
Affiliation:
1HarlandHall
The Stables,
Ranbury Ring,
London Road
Poulton,
Cirencester,
GL7 5HN England
1
2Kellogg European Headquarters
Lakeshore Drive,
Airside Business Park,
Swords,
Co Dublin
Eire
2
HarlandHall
The Stables,
Ranbury Ring,
London Road
Poulton,
Cirencester,
GL7 5HN England
Author responsible for correspondence:
Jolene McMonagle
Short title/running head:
Effect of wheat bran fibre on blood triglycerides
Key words:
wheat bran, blood lipids, triglycerides, cardiovascular risk
Text word count: 247
Abstract
Objective:
To review the evidence relating to wheat bran fibre intake (WBF) and their effect on blood
lipids.
Design:
Systematic review and meta-analysis of intervention studies reporting WBF intake and blood
lipids, specifically triglycerides concentrations (TAG).
Setting:
Medline and other scientific databases were searched for the period 1966–2011 to produce a
full reference list of articles for review.
Methods:
A matrix of eligibility for study inclusion was established; 13 intervention studies conducted
with 281 broadly healthy adults met the criteria and were retained for further analysis. Using
standard meta-analysis techniques, standard mean difference in blood lipids following WBF
intake were calculated. Meta-regression analysis of added WBF intake on mean difference
blood TAG was also conducted.
Results
Diets incorporating an average of 17.3 g/day WBF resulted in a reduced standard mean
difference in blood TAG of 0.178 mmol/L, (95% CI -0.303, -0.053), P=0.005. There was
some evidence of an inverse dose-response relationship between added wheat bran intake (g
dietary fibre /day) and net change in mean TAG, which failed to reach statistical significance,
P =0.066.
There were minor changes and significant heterogeneity in other blood lipid data, except for
very low density lipoprotein (VLDL) cholesterol, which on the basis of limited data from
four studies was reduced by -0.102 mmol/L (95% CI -0.162, -0.043), P=0.001.
Conclusion
The addition of 17.3g /day WBF to the diet significantly lowered blood TAG by 0.178
mmol/L, equivalent to 8.6% reduction compared to baseline, without adverse effects on other
blood lipids.
!
"#
Introduction
MetS and personalised nutrition
Elevated plasma TAG concentrations and low levels of high-density lipoprotein (HDL)
cholesterol are recognised cardiovascular risk factors, although attention is usually focussed
on low density lipoprotein (LDL) cholesterol as a prime risk factor. The pivotal role that
plasma TAG concentrations play in lipid metabolism is the subject of a recent consensus
statement from the American Heart Association (AHA), who after reviewing the evidence,
has confirmed that blood TAG, more appropriately, represent a biomarker of CHD risk rather
than an independent risk factor 1. However, it is recognised that in some individuals at risk
from cardiovascular disease (CVD) or insulin resistance (Ri), low density lipoprotein (LDL)
-cholesterol levels may not be elevated, but TAG levels are raised. In recognition of the
importance of TAG, the AHA scientific statement suggests the following new designations:
optimal fasting TAG levels are defined as <100 mg/dL (1.13 mmol/L), as a parameter of
metabolic health, borderline high fasting TAG levels are 150 to 199 mg/dL ( 1.7 to 2.2
mmol/L), high levels are 200 to 499 mg/dL ( 2.3 to 5.6 mmol/L) and very high levels ≥500
mg/dL (5.6 mmol/L). This reduction of the upper "normal" level of TAG to (≥ 1.7 mmol/L)
was also recently endorsed in a critical appraisal of the evidence relating to elevated levels of
triglyceride-rich lipoproteins (TRLs) by the European Atherosclerosis Society Consensus
Panel 2, who also recommended the targeting of elevated TAG (≥ 1.7 mmol/L) as a marker of
TRL 3.
An extensive collaborative review of 101 studies identified that those with a genetic tendency
for high levels of triglycerides also had a greater risk of heart disease, providing evidence for
a causal association between triglyceride-mediated pathways and CHD 4.
Approximately 31% of the adult US population has a triglyceride level > 1.7mmol/L with no
appreciable change between the National Health and Nutrition Examination Surveys
(NHANES) of 1988–1994 and 1999–2008 data 1. Where increases in TAG have been
observed, this is primarily in younger age groups (20 to 49 years old), and overall, TAG
levels continue to be higher than in less industrialized societies 1. Taking a longer
perspective, mean TAG levels have risen since 1976, associated with exponential increases
in obesity, insulin resistance, and type 2 diabetes, while LDL cholesterol have not changed.
Quantification of the association between serum TAG and the risk of CHD was recently
undertaken using data from the European Prospective Investigation of Cancer (EPIC)-
Norfolk and Reykjavik studies 5. Two separate nested case-control comparisons were
conducted involving 3582 incident cases of fatal and nonfatal CHD and 6175 controls
selected from among the 44,237 men and women screened in the population studies. The
long-term stability of log-triglyceride values (within-person correlation coefficients of 0.64
(95% CI 0.60, 0.68) and 0.63 (95% CI 0.57, 0.70) over 4 and 12 years respectively) was
similar to those of blood pressure and total serum cholesterol. After adjustment the strength
of the association was attenuated, and the adjusted odds ratio (OR) for CHD was 1.76 (95%
CI 1.39, 2.21) in the Reykjavik study and 1.57 (95% CI 1.10, 2.24) in the EPIC-Norfolk
study, when the top third of individuals were compared with those in the bottom third of
values. A meta-analysis involving a total of 10,158 CHD cases from 262,525 participants in
29 studies also indicated an increased risk of CHD with elevated blood TAG; adjusted OR
was 1.72; (95% CI 1.56, 1.90) 5. Further epidemiological evidence is provided by a cohort of
1232 high-risk men aged 40-49 y followed for 23 years in the Oslo Diet and Antismoking
Trial. In this study normalising TAG, by lifestyle interventions in men with elevated TAG,
was associated with an reduced risk of ischemic heart disease (IHD) events; hazard ratio of
IHD events was 0.56 (95% CI 0.34, 0.93; P = 0.027) 6.
While an association between elevated TAG and CHD exists, the extent to which it is
independent of other risk factors of CHD remains less clear. For example, the treatment of
elevated TAG levels is often undertaken with interrelated lifestyle changes such as weight
loss; a 5% to 10% reduction in body weight may result in a triglyceride-lowering response of
20% with both factors contributing to the reduction in CHD risk 1. Elevated blood TAG is
also evident in Type 2 diabetics and high TAG levels accompanying either normal or
impaired fasting glucose can predict its development, as well as being one of the key risk
factors for the Metabolic Syndrome.Maintenance of normal blood concentration of TAG is
clearly a beneficial physiological effect and effective dietary management of elevated TAG
levels is an area that requires further attention. Contrary to traditionally-held opinion, it has
been shown that the long-term within-individual variability of TAG is no greater than that of
other lipid fractions 7; as such, it could provide a target for monitoring and intervention.
While an increase in fibre intake is considered desirable in diets for both diabetics and those
at risk from CHD, the focus of research has tended to be on the extent to which soluble
sources of fibre 8-11 or mixtures of whole-grain cereals can contribute 12. The objective of this
study was however, to investigate the role that can be played by well-characterised less
soluble cereal fibre, WBF, in modifying blood lipids specifically, blood TAG. In Western
populations, wheat is the predominant source of fibre or non-starch polysaccharide (NSP)
intake 13-15. Wheat bran has long been recognised as beneficial in gut transit and faecal
bulking16, although in studies related to blood lipid metabolism it has largely been considered
inert and has often been used as a control. A further objective of this study was to establish if
this assumption was valid.
Materials and methods
Searching
Computerised scientific publication databases were searched. The search was focused on
Medline (www.ncbi.nlm.nih.gov/entrez/query.fcgi) for the period January 1966 through to
November 2011 and was confined to human studies but no language restriction was imposed.
It was complemented by searches in EMBASE and hand search of key papers and references
cited in identified articles. In addition, the reference lists in identified papers were scrutinised
for further studies. Initial search terms were ‘wheat bran' or 'wheat fibre (fiber)' or 'cereal
bran or fibre (fiber)' or 'whole wheat' and 'blood or plasma or serum triglycerides' or
'cholesterol' or 'blood or plasma or serum lipids'. The search strategy was applied to titles and
abstracts only, in order to identify studies where interventions related WBF were the primary
intervention and not the control or placebo.
Data abstraction and quality assessment
The review of identified papers was conducted according to the QUORUM principles17 (Fig.
1). Studies were retained where the introduction of wheat bran fibre was a primary
intervention. Studies could be either crossover or parallel in design and should compare
WBF to baseline or a suitable control. WBF could be sourced from bran flakes or bran-rich
foods or whole wheat foods. Subjects were broadly healthy volunteers were healthy or mildly
hypercholesterolaemic, with average weight loss <1 kg/week and average BMI < 35; study
duration was a minimum of 3 weeks. Studies were excluded when participants were taking
lipid-lowering drugs or antihypertensive medication. The fibre content of the supplement
should be reported and measured using the method of the Association of Official Analytical
Chemists (AOAC), the Englyst method for non-starch polysaccharides (NSP), Southgate
method or a recognised method of dietary fibre analysis. Studies using a blend of different
cereal fibres or multiple cereals such as undefined wholegrains were excluded, as were
studies reporting fibre determined by crude fibre analysis.
Fig. 1 near here
The key characteristics of the studies were abstracted and the findings collated, which
included: identification of the number of subjects, gender, age, duration of study,
measurements of blood lipids, macronutrient content of the diet, definition of fibre and
method of assessment of intake. The data abstracted were subject to quality assessment in
three main areas: recruitment and flow of subjects through the study, dietary assessment and
treatment and reporting of data.
$%& ' "
" $() " %"" *+,- ,+,- %"" %
."" . " "&& /0,+,1 %""# 2 ."
&"-"%#
Statistical methods
2 . /3#+#1 4 % % " "& ."
"" 4 . % &&"" " &
"4""-%4""
% 6 ' &&% 7 6 ." /8!1
""#*""*98%9
:# $ % ."" ' ; %
%%&"4%".4 %
" "& "."# 2- " %
&%&5<=>
/ 6?1 % $()#Comprehensive Meta-Analysis
software (Biostat, Englewood, NJ 07631, USA) was used for all statistical analysis
Results
Trial flow
Fig. 1 outlines the results from the reported review process. The search identified 116 papers;
when abstracts were scanned and exclusion criteria applied, this resulted in 31 potentially
relevant studies. After reading the full articles, 14 treatment arms from 13 studies were
retained for further analysis 18-30. In addition to reporting some measure of blood lipids and
WBF intake, retained studies measured macronutrient intake. This could be reported as either
total intake, or the macronutrient content of the supplement where macronutrient content of
the background diet was kept constant. Studies were not retained for further analysis for the
following reasons: nutrient intake not matched or significantly different at baseline 31-34, no
nutrient intake data 35-37, primary objective not related to WBF or wheat bran treatment
inadequately characterised 38-42, subjects not healthy 43, inadequate study duration 22, 44 and
data values not presented or presented as figures unsuitable for further analysis or pooled data
presented 30, 45-46.
Study characteristics
Details of the 13 retained papers that contained studies measuring blood lipids and with a
WBF intervention are shown in Table 1.
Table 1 near here
Retained studies included 8 randomised crossover studies (RX), 2 randomised controlled
parallel design (RCP) and 3 phased interventions, with and without WBF. Two studies were
single-blinded 19, 47, and one study double-blinded 24. Studies were conducted with 281 adult
male and females aged 18-73 years, most of whom were described as healthy, but included
mild hypercholesterolaemics and hypertensives. Study length ranged from 3-12 weeks, mean
4.6 weeks. The range of additional WBF intake was 10-22g /day. A number of analytical
techniques were used to measure fibre, most prevalent were AOAC and Southgate, which
can be expected to give similar results 48. Three studies measured NSP and by reference to
extensive data, these values were converted to be more similar to fibre determined by AOAC
by use of a conversion factor of 1.2, known to be appropriate for WBF. All studies apart from
two, reported macronutrient and energy intake 20, 26. The majority of studies were crossover
in design, the primary comparison made, was end of treatment values compared to control
end values. This approach was also used for the parallel studies, which were corrected for
baseline; for phased intervention studies end of intervention values were compared to
baseline. The average baseline blood TAG level was 1.52 mmol/L, with subjects from 2
treatment arms classified as borderline high 18, 27 and 2 classified as high 22.
Analysis of main outcomes
Thirteen treatment arms from 12 studies provided numerical data for the primary outcome,
blood TAG; when the data was pooled the inclusion of WBF in the diet resulted in a
significant standard mean difference in TAG of -0.178 mmol/L (95% CI -0.303, -0.053),
P=0.005. Heterogeneity was not evidence in the dataset, P =0.24. See Fig. 2. The inclusion of
an average of 17.3g WBF led to a mean reduction in TAG of 8.6% compared to baseline, but
when the mean reduction was calculated using the standard mean difference data, the
reduction compared to baseline was equivalent to 22%.
Figure 2 near here.
Figure 3 near here.
Meta regression was conducted to determine whether a dose-response relationship existed
between wheat fibre intake and net change in mean TAG. From Fig. 3, it can be seen that
there is some evidence of an inverse association between WBF intake (g dietary fibre/day)
and the reduction in TAG, however the relationship just failed to reach statistical significance,
P =0.066.
Publication bias has been assessed by two methods, funnel plot of the standard error by
standard difference in mean TAG and Classic fail-safe N. The funnel plot is a plot of a
measure of study size (usually standard error) on the vertical axis as a function of effect size
on the horizontal axis, Fig. 4. Large studies appear toward the top of the graph, and tend to
cluster near the mean effect size. Smaller studies appear toward the bottom of the graph, and
(since there is more sampling variation in effect size estimates in the smaller studies) will be
dispersed across a range of values. In the absence of publication bias the studies are
distributed symmetrically about the combined effect size. This is broadly the case as shown in
Fig. 4. From this plot it can be seem that there is good symmetry around the centre line and
good distribution of the studies from top to bottom, there is a small indication of bias due to a
cluster of studies on the mid-left of the centre line. However when Classic fail-safe N is
calculated by incorporating data from 13 treatment arms, which yield a z-value of - 3.56 and
corresponding 2-tailed P-value of 0.0004. The fail-safe N is 30. This means that 30 'null'
studies would need to be located in order for the combined 2-tailed p-value to exceed 0.050
or there would be need to be 2.3 missing studies for every observed study for the effect to be
nullified indicating little evidence of bias.
Figure 4 near here.
When data relating to total, LDL- and HDL- cholesterol were pooled there was little effect on
these parameters with total cholesterol unchanged, a small reduction in LDL- cholesterol and
an increase in HDL- cholesterol. In all three datasets there was evidence of high degree of
heterogeneity (P<0.001) (data not shown).
Four studies 18, 20-21, 29, reported data related very low density lipoprotein (VLDL) cholesterol,
in all cases VLDL was reduced and when pooled, the simple mean difference was -0.102
mmol/L (95% CI -0.162, -0.043), P=0.001. Heterogeneity was not evident (P=0.058), but as
of borderline significance, a random effects analysis was also conducted, with little effect on
the outcome (-0.106 mmol/L, 95% CI -0.200, -0.011; P=0.029).
Discussion
This is the first analysis that has specifically investigated the role of WBF intake on blood
TAG. The pooling of data from trials where there was an average intake of 17.2g dietary fibre
from wheat bran resulted in an overall significant effect on blood TAG of -0.178 mmol/L
(95% CI -0.303, -0.053) (Fig. 2) equivalent to a reduction compared to baseline of ca 9%.
From the meta regression it can be calculated that each 10g intake of dietary fibre intake was
associated with a reduction in TAG of approximately 0.1 mmol/L. The reduction in TAG was
associated with little effect on other blood lipids, with the exception of VLDL, where there
was also indication of a reduction in this lipid material. Previous assumptions that wheat bran
has little effect on blood cholesterol appear to be valid, although in respect of an effect on
blood TAG this clearly is open to question.
Nutrition modifications that can effect TAG levels have focussed on reducing overall energy
(e) intake, as it is recognised that weight loss has a beneficial effect on blood TAG 49.
Furthermore the magnitude of decrease in TAG is directly related to the amount of weight
loss and, by means of a meta-analysis, it has been estimated that for each kilogram of weight
loss, a decrease in TAG of 1.9% results 50,51. In this analysis, studies were selected where
weight loss was minimal and using the relationship described above by Anderson et al. 51, it
can be calculated that to account for the reported 8.6% reduction in TAG, there would have
had to have been a 4.5kg loss in weight, which was not the case.
Other aspects of nutrient intake that can influence TAG levels are total fat and available
carbohydrate intake 52. In a meta-analysis of 60 studies, a 1 % isoenergetic replacement of
saturated, monounsaturated or polyunsaturated fat with carbohydrate resulted in significant
increases in fasting TAG levels of 0.021, 0.019 and 0.026 mmol/L respectively, all P<0.001,
indicating a benefit from replacing available carbohydrate with fat. A similar effect was
reported when moderate fat diets (32.5% to 50%e from fat) were compared to lower-fat diets
(18% to 30%e from fat) with a resulting decrease in TAG of 0.1 mmol/L (range from -0.07
to - 0.14 mmol/L, P<0.00001) with the moderate fat diet 53. In subjects with diabetes the
moderate fat diet intervention led to an even greater reduction in TAG 53.
Within this database of studies macronutrient content of baseline and intervention was
matched to varying degrees. There was no significant differences in the macronutrient
content reported for retained studies, however there was a difference in fat intake between
baseline and the wheat and barley interventions of 20 and 19g respectively in one study 25 and
the supplement used in one study increased protein intake by ca 60g and reduced available
carbohydrate intake by ca 70g 22. Exclusion of these three treatments from the analysis
resulted in a reduction in mean TAG which was similar to the dataset as a whole (-0.166
mmol/L; 95% CI -0.312, -0.021; P=0.025). It therefore appears likely that the fibre or some
component of the bran is the causal agent for the reduction that we have reported.
The role of fibre intervention on blood TAG is less well documented particularly in non-
diabetic subjects, although fixed-effect meta-analyses techniques have been used to obtain
mean estimates of changes in blood lipids following dietary intervention in diabetics 54. High
carbohydrate, high fibre diets compared to moderate carbohydrate, low fibre diets were
associated with lower values for fasting, postprandial and average plasma glucose, total, LDL
and HDL-cholesterol and TAG. Overall indications were that high intakes of dietary fibre
(≥20 grams/1000 kcal) in the context of moderate or high carbohydrate diets led to improved
serum lipoproteins, with reported reductions in TAG of 8.3-12.8% 54. In this analysis, total
dietary fibre intake / 1000 kcal could be estimated in ten treatments 18-25, 47 and ranged from 8
- 24g/ 1000 kcal, while added dietary fibre from wheat bran was on average 17.3g (range 7-
36g ). From this analysis it can be seen that the addition of 17.3g dietary fibre from wheat
bran was associated with a reduction in TAG of 8.6%, not dissimilar to that reported for
diabetics 54.
$% "."%%.%
6>"$()#$%<+3
% " "& " & 4
""6>&&"4"
4"" 45="#!%" - ".4
$&."$()
"6-""6 -""6 #(
" . $() " 6
&%%83
">#
Wheat bran also is a source of minerals, vitamins and phenolic compounds. These phenolic
compounds provide the plant's defence system and include derivatives of benzoic and
cinnamic acid, the most extensively studied of which is ferulic acid 14. There is evidence that
intestinal microbes can release ferulic acid and other phenolics from the bran, hence these
substances or their metabolites are bioavailable and may be physiologically active, although
the mechanisms involved require further investigation 14. It is suggested that the
cardiovascular benefits may be related to folate, magnesium, vitamin B-6, vitamin E or serum
levels of enterlactone rather than the fibre per se 57.
In a recent analysis of the Nurses' Health Study, 7822 women with type 2 diabetes were
assessed for the risks of all cause and CVD mortality. After adjustment for age, lifestyle and
dietary risk factors, the strongest association that remained was an inverse association
between cereal bran intake and CVD-specific mortality. The relative risk across fifths of bran
intake were 1.0, 0.95, 0.80, 0.76 and 0.65 respectively ( P for trend = 0.04) 58. The
relationship was evident after adjustment, whereas no significant associations were evident
after adjustment, for whole-grain intake, for cereal fibre or germ intake. While cereal bran
will include other sources cereal fibre, it should be recalled that in both US and UK
populations wheat is the predominant source of whole grain cereals in the diet and is likely to
comprise at least half of cereal bran 14-15. A beneficial association between CHD and whole
grains intake in the US Health Professionals Survey also identified that the bran component
could be a key factor in the relationship 59. The mechanism responsible for this association
between cereal bran and CVD has not been identified and it conceivable reduction in blood
TAG may be a contributing factor.
@0,+,%""""&%%"
"4%"40,+,%".&"
40,+,&""444
de novo %& "& % $()
%# ( 0,+, $() " "" %
">"%4%44%%"",+,#*%
""."40,+,%"" $() &%
%"%"&&&&6"">480+#
There are a number of limitations in this analysis, the quality of identified studies was
variable, few studies were blinded, the nature of the control was variable and a number of the
studies compared wheat with oats, where wheat bran it could perhaps be implied, was a
control treatment. The analytical determination of dietary fibre was undertaken principally by
AOAC technique, but NSP (adjusted) and other measures were also used giving rise to
another source of variation. The presentation of WBF to subjects took a variety of different
forms including bran supplements breakfast cereals, bread, biscuits, muffins, wheat whole-
grain foods and supplements. The effect which food processing techniques employed during
the manufacture of the WBF foods have on bioavailailabilty of WBF components critical for
the mechanism of action is uncertain.
Nevertheless the inclusion of a modest intake of wheat bran resulted in a small TAG lowering
effect, which may contribute to reduction of cardiovascular risk. Overall, its addition to
optimisation of nutrition interventions, such as reductions in available carbohydrate,
restriction in added sugars and fructose, reduction in trans and saturated fatty acid intake and
optimal consumption of long-chain omega-3 fatty acids can contribute to a TAG-lowering
effect that ranges between 20% and 50% 1.
Acknowledgements
The provision of a unconditional grant from the Kellogg Group of European Companies is
gratefully acknowledged.
Table 1 Details of the intervention studies included in the present systematic review and analysis
Author
Studies
Year
Control Intervention
Food/constituent
Daily intake
(constituent)
Fibre
intake
Fibre
method
Interve
ntion
time
Study
type
Sex
N
Population
Anderson
1991 18
Control diet
41% e fat, 16%
e protein, 43% e
CHO 18g DF all
foods prepared
& eaten in
metabolic ward
Control diet +
either wheat or oat
bran
40g wheat bran
from breakfast
cereal + wheat bran
muffins
34g
wheat
DF
7.8g
soluble
F
Total
dietary
fibre as
USDA
data-base
21days RCT P 20 M Hypocholesterolae
mic >5.2 mmol/L
TC, TAG <3.4
mmol/L, BMI
>28.7; 38-73 y, no
medication, but 14
had diagnoses of
hypertension, CHD
or CVD
Bremer
199119
Phase II AHA
diet to stabilise
blood lipids
Bread with oat bran
or wheat
15.3g
wheat
DF
AACC 4wk RT SB
X
5 M/
7F
Hyperlipidaemics,
TC 5.7-9 mmol/L ,
38-66 y
Gariot
198620
Control diet all
foods prepared
& eaten in
metabolic unit
+20g wheat bran
prepared as bread
+20g
WB @
59%F
11.8g
wheat
F
South-
gate
7 wk PIT 4 M Healthy
Giacco
201021
Refined wheat Whole wheat
+13.3g F ex whole
wheat
+13.3g
wheat
F
AOAC 3wk RCT
X
12 M/
3 F
Healthy, BMI
27.4+/-3.0,
54.5 y +/-7.6
Jenkins
197523
Control diet all
foods prepared
& eaten in
metabolic unit
Wheat bran +36g
wheat
F
South-
gate
3wk RT X 6 M Healthy
Jenkins
1999 22
Study 1
metabolic study.
Control low
fibre bread.
Wheat bran
medium or ultra
fine +gluten
Wheat bran and
gluten in prepared
breads
+19g
wheat
DF
AOAC 1mo RCT
X
16M/
8F
Healthy (1 F on
HRT) BMI 17.9-
31.5,
35-72y
Kestin White bread Bread with 12g +12g/ NSP 4wk RCT 24M Mild
1990 24 Low fibre diet
<12g NSP
wheat bran day
wheat
F
DB X
Latin
square
hypercholesterolae
mic
McIntosh
1991 25
No control 2
treatments
Bread/muesli/spagh
etti/biscuits with
wheat or barley
fibre
+17.2g
/day
NSP
NSP 4wk RT X 21M Mild
hypercholesterolae
mic
30-59 y
Moore
1984 26
With and
without bran
Wheat bran
0.15g/kg/Bwt
+7.2 to
11.9g /
day
South-
gate
6wk PIT 3 M/
4 F
Healthy 18-22 y
Rave 2007
27
No control 2
treatments
200g/day
Balantose™
(Cargill) Double
fermented whole
grain wheat
+21.4g/
day
wheat
F
AOAC 4 wk RT X 13M/
18F
Free living obese,
BMI >29 to
< 40 kg/m2 with
elevated blood
glucose >6·1 and
≤ 7·1 mmol/L
Tighe 2010
47
Refined diet
intake 10-12g
NSP
3 servs whole-grain
wheat foods
+6.2g/
day
wheat
F
NSP 12wk RCT
SB P
186
M/F
Healthy middle
aged
van Berge-
Henegouw
en 1979 29
Habitual diet Coarse wheat bran
0.5g/kg/Bwt +33.5
to 37.8g wheat
bran/day
+20.8g
DF
wheat
F
58.3%
DF
Van
Soest
4wk PIT 7 M Healthy, 18-24 y
Vuksan
2011 30
No control, 3
treatments
Fibre from
breakfast cereals or
sprinkled
14g DF/ 4184 kJ
from All Bran/Bran
Buds + viscous
fibre
+12g
DF
from
wheat
F
AOAC? 21 d RT X 12 M/
11 F
Healthy, LDL-C
2.9 mmol/L,
35 (SD 12) y
Abbreviations: NG - not given, M male, F female, wk week, RCT - randomised controlled
trial; P - Parallel; X - crossover study; PIT - Prospective intervention trial; DB - Double blind;
SB - Single blinded; F fibre; DF dietary fibre; NSP non starch polysaccharides; BWt body
weight; servs servings; C= control; I = intervention;
References
[1] Miller M, Stone NJ, Ballantyne C, et al. (2011) Triglycerides and cardiovascular disease: a scientific
statement from the American Heart Association Circulation 123, 2292-333.
[2] Abdel-Maksoud M, Sazonov V, Gutkin SW, et al. (2008) Effects of modifying triglycerides and
triglyceride-rich lipoproteins on cardiovascular outcomes J Cardiovasc Pharmacol 51, 331-51.
[3] Chapman MJ, Ginsberg HN, Amarenco P, et al. (2011) Triglyceride-rich lipoproteins and high-density
lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management
Eur Heart J 32, 1345-61.
[4] (2010) Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies The
Lancet 375, 1634-9.
[5] Sarwar N, Danesh J, Eiriksdottir G, et al. (2007) Triglycerides and the risk of coronary heart disease:
10,158 incident cases among 262,525 participants in 29 Western prospective studies Circulation 115, 450-8.
[6] Ellingsen I, Hjermann I, Abdelnoor M, et al. (2003) Dietary and antismoking advice and ischemic heart
disease mortality in men with normal or high fasting triacylglycerol concentrations: a 23-y follow-up study Am
J Clin Nutr 78, 935-40.
[7] Sarwar N, Sattar N (2009) Triglycerides and coronary heart disease: have recent insights yielded
conclusive answers? Curr Opin Lipidol 20, 275-81.
[8] Brown L, Rosner B, Willett WW, et al. (1999) Cholesterol-lowering effects of dietary fiber: a meta-
analysis Am J Clin Nutr 69, 30-42.
[9] Talati R, Baker WL, Pabilonia MS, et al. (2009) The effects of barley-derived soluble fiber on serum
lipids Annals of family medicine 7, 157-63.
[10] Pins JJ, Kaur H, Dodds E, et al. (2007) The effects of cereal fibers and barley foods rich in beta-glucan
on cardiovascular disease and diabetes risk. In Whole grains and health. Marquart L, Jacobs DR Jr, McIntosh
GH, Poutanen K, Reicks M eds. London: Blackwell, 2007: 75-85.
[11] Ripsin CM, Keenan JM, Jacobs DR, Jr., et al. (1992) Oat products and lipid lowering. A meta-analysis
Jama 267, 3317-25.
[12] Mellen PB, Walsh TF, Herrington DM (2007) Whole grain intake and cardiovascular disease: A meta-
analysis Nutr Metab Cardiovasc Dis.
[13] Lang R, Thane CW, Bolton-Smith C, et al. (2003) Consumption of whole-grain foods by British adults:
findings from further analysis of two national dietary surveys Public Health Nutr 6, 479-84.
[14] Jonnalagadda SS, Harnack L, Liu RH, et al. (2011) Putting the whole grain puzzle together: health
benefits associated with whole grains--summary of American Society for Nutrition 2010 Satellite Symposium J
Nutr 141, 1011S-22S.
[15] Thane CW, Jones AR, Stephen AM, et al. (2007) Comparative whole-grain intake of British adults in
1986-7 and 2000-1 Br J Nutr 97, 987-92.
[16] Cummings JH (1993) The Effect of Dietary Fiber on Fecal Weight and Composition. In CRC
Handbook of Dietary Fiber in Human Nutrition, 2nd Edition, pp. 263-349 editor^editors|]. City|: Publisher|.
[17] Clarke M (2000) The QUORUM statement Lancet 355, 756-7.
[18] Anderson JW, Gilinsky NH, Deakins DA, et al. (1991) Lipid responses of hypercholesterolemic men to
oat-bran and wheat-bran intake Am J Clin Nutr 54, 678-83.
[19] Bremer JM, Scott RS, Lintott CJ (1991) Oat bran and cholesterol reduction: evidence against specific
effect Aust N Z J Med 21, 422-6.
[20] Gariot P, Digy JP, Genton P, et al. (1986) Long-term effect of bran ingestion on lipid metabolism in
healthy man Ann Nutr Metab 30, 369-73.
[21] Giacco R, Clemente G, Cipriano D, et al. (2010) Effects of the regular consumption of wholemeal
wheat foods on cardiovascular risk factors in healthy people Nutr Metab Cardiovasc Dis 20, 186-94.
[22] Jenkins DJ, Kendall CW, Vuksan V, et al. (1999) Effect of wheat bran on serum lipids: influence of
particle size and wheat protein J Am Coll Nutr 18, 159-65.
[23] Jenkins DJ, Hill MS, Cummings JH (1975) Effect of wheat fiber on blood lipids, fecal steroid excretion
and serum iron Am J Clin Nutr 28, 1408-11.
[24] Kestin M, Moss R, Clifton PM, et al. (1990) Comparative effects of three cereal brans on plasma lipids,
blood pressure, and glucose metabolism in mildly hypercholesterolemic men Am J Clin Nutr 52, 661-6.
[25] McIntosh GH, Whyte J, McArthur R, et al. (1991) Barley and wheat foods: influence on plasma
cholesterol concentrations in hypercholesterolemic men Am J Clin Nutr 53, 1205-9.
[26] Moore DJ, White FJ, Flatt PR, et al. (1985) Beneficial short-term effects of unprocessed wheat bran on
lipid and glucose metabolism in man Hum Nutr Clin Nutr 39, 63-7.
[27] Rave K, Roggen K, Dellweg S, et al. (2007) Improvement of insulin resistance after diet with a whole-
grain based dietary product: results of a randomized, controlled cross-over study in obese subjects with elevated
fasting blood glucose Br J Nutr 98, 929-36.
[28] Tighe P, Duthie G, Vaughan N, et al. (2010) Effect of increased consumption of whole-grain foods on
blood pressure and other cardiovascular risk markers in healthy middle-aged persons: a randomized controlled
trial Am J Clin Nutr 92, 733-40.
[29] van Berge-Henegouwen GP, Huybregts AW, van de Werf S, et al. (1979) Effect of a standardized wheat
bran preparation on serum lipids in young healthy males Am J Clin Nutr 32, 794-8.
[30] Vuksan V, Jenkins AL, Rogovik AL, et al. (2011) Viscosity rather than quantity of dietary fibre predicts
cholesterol-lowering effect in healthy individuals Br J Nutr 106, 1349-52.
[31] Anderson JW, Riddell-Mason S, Gustafson NJ, et al. (1992) Cholesterol-lowering effects of psyllium-
enriched cereal as an adjunct to a prudent diet in the treatment of mild to moderate hypercholesterolemia Am J
Clin Nutr 56, 93-8.
[32] Connell AM, Smith CL, Somsel M (1975) Absence of effect of bran on blood-lipids Lancet 1, 496-7.
[33] Reyna-Villasmil N, Bermudez-Pirela V, Mengual-Moreno E, et al. (2007) Oat-derived beta-glucan
significantly improves HDLC and diminishes LDLC and non-HDL cholesterol in overweight individuals with
mild hypercholesterolemia Am J Ther 14, 203-12.
[34] Jenkins DJ, Kendall CW, Marchie A, et al. (2002) Dose response of almonds on coronary heart disease
risk factors: blood lipids, oxidized low-density lipoproteins, lipoprotein(a), homocysteine, and pulmonary nitric
oxide: a randomized, controlled, crossover trial Circulation 106, 1327-32.
[35] Durrington P, Wicks AC, Heaton KW (1975) Letter: Effect of bran on blood-lipids Lancet 2, 133.
[36] Heaton KW, Pomare EW (1974) Effect of bran on blood lipids and calcium Lancet 1, 49-50.
[37] McDougall RM, Yakymyshyn L, Walker K, et al. (1978) Effect of wheat bran on serum lipoproteins
and biliary lipids Can J Surg 21, 433-5.
[38] Bloedon LT, Balikai S, Chittams J, et al. (2008) Flaxseed and cardiovascular risk factors: results from a
double blind, randomized, controlled clinical trial J Am Coll Nutr 27, 65-74.
[39] Davy BM, Melby CL, Beske SD, et al. (2002) Oat consumption does not affect resting casual and
ambulatory 24-h arterial blood pressure in men with high-normal blood pressure to stage I hypertension J Nutr
132, 394-8.
[40] Romero AL, Romero JE, Galaviz S, et al. (1998) Cookies enriched with psyllium or oat bran lower
plasma LDL cholesterol in normal and hypercholesterolemic men from Northern Mexico J Am Coll Nutr 17,
601-8.
[41] Salvioli G, Lugli R, Pradelli JM (1985) Cholesterol absorption and sterol balance in normal subjects
receiving dietary fiber or ursodeoxycholic acid Dig Dis Sci 30, 301-7.
[42] Winreich J, Pedersen O, Dinesen K (1977) Role of bran in normals. Serum levels of cholesterols,
triglyceride, calcium and total 3 alpha-hydroxycholanic acid, and intestinal transit time Acta Med Scand 202,
125-30.
[43] Jenkins DJ, Kendall CW, Augustin LS, et al. (2002) Effect of wheat bran on glycemic control and risk
factors for cardiovascular disease in type 2 diabetes Diabetes Care 25, 1522-8.
[44] Kashtan H, Stern HS, Jenkins DJ, et al. (1992) Wheat-bran and oat-bran supplements' effects on blood
lipids and lipoproteins Am J Clin Nutr 55, 976-80.
[45] Lewis S, Bolton C, Heaton K (1996) Lack of influence of intestinal transit on oxidative status in
premenopausal women Eur J Clin Nutr 50, 565-8.
[46] Munoz JM, Sandstead HH, Jacob RA, et al. (1979) Effects of some cereal brans and textured vegetable
protein on plasma lipids Am J Clin Nutr 32, 580-92.
[47] Tighe P, Duthie G, Vaughan N, et al. (2010) Effect of increased consumption of whole-grain foods on
blood pressure and other cardiovascular risk markers in healthy middle-aged persons: a randomized controlled
trial Am J Clin Nutr.
[48] Devries JW (2004) Dietary fiber: the influence of definition on analysis and regulation J AOAC Int 87,
682-706.
[49] Van Gaal LF, Mertens IL, Ballaux D (2005) What is the relationship between risk factor reduction and
degree of weight loss? European Heart Journal Supplements 7, L21-L6.
[50] Poobalan A, Aucott L, Smith WC, et al. (2004) Effects of weight loss in overweight/obese individuals
and long-term lipid outcomes--a systematic review Obes Rev 5, 43-50.
[51] Anderson JW, Konz EC (2001) Obesity and disease management: effects of weight loss on comorbid
conditions Obes Res 9 Suppl 4, 326S-34S.
[52] Mensink RP, Zock PL, Kester AD, et al. (2003) Effects of dietary fatty acids and carbohydrates on the
ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60
controlled trials Am J Clin Nutr 77, 1146-55.
[53] Cao Y, Mauger DT, Pelkman CL, et al. (2009) Effects of moderate (MF) versus lower fat (LF) diets on
lipids and lipoproteins: a meta-analysis of clinical trials in subjects with and without diabetes J Clin Lipidol 3,
19-32.
[54] Anderson JW, Randles KM, Kendall CW, et al. (2004) Carbohydrate and fiber recommendations for
individuals with diabetes: a quantitative assessment and meta-analysis of the evidence J Am Coll Nutr 23, 5-17.
[55] Ylonen K, Saloranta C, Kronberg-Kippila C, et al. (2003) Associations of dietary fiber with glucose
metabolism in nondiabetic relatives of subjects with type 2 diabetes: the Botnia Dietary Study Diabetes Care 26,
1979-85.
[56] Ludwig DS, Pereira MA, Kroenke CH, et al. (1999) Dietary fiber, weight gain, and cardiovascular
disease risk factors in young adults JAMA 282, 1539-46.
[57] De Moura FF. Whole Grain Intake and Cardiovascular Disease and Whole Grain Intake a Diabetes a
Review. Bethesda: Life science Research Office, 2008.
[58] He M, van Dam RM, Rimm E, et al. (2010) Whole-grain, cereal fiber, bran, and germ intake and the
risks of all-cause and cardiovascular disease-specific mortality among women with type 2 diabetes mellitus
Circulation 121, 2162-8.
[59] Jensen MK, Koh-Banerjee P, Hu FB, et al. (2004) Intakes of whole grains, bran, and germ and the risk
of coronary heart disease in men Am J Clin Nutr 80, 1492-9.